Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Anticancer Drugs. 2013 Sep;24(8):769-80. doi: 10.1097/CAD.0b013e328363adc5.
Approximately 75% of patients with breast cancer present hormone receptor-positive tumors. This subtype of breast cancer initially shows a high overall response rate to hormonal treatments. However, resistance eventually develops, resulting in tumor progression. The PI3K/Akt/mTOR pathway regulates several cellular functions in cancer such as cell growth, survival, and proliferation. In addition, a high activation level of the PI3K/Akt/mTOR pathway is related to resistance to conventional chemotherapy and hormone therapy. The mTOR inhibitor everolimus, in combination with hormonal treatments, has led to excellent results in progression-free survival in patients with metastatic breast cancer resistant to hormone therapies. Therefore, everolimus has entered the National Comprehensive Cancer Network (NCCN) guidelines 2012 and its combination with exemestane was approved recently by the US Food and Drug Administration and the European Medicines Agency. This is the first time that a drug will have been approved for the restoration of hormone sensitivity in breast cancer.
约 75%的乳腺癌患者表现出激素受体阳性肿瘤。这种亚型的乳腺癌最初对激素治疗有很高的总体反应率。然而,最终会产生耐药性,导致肿瘤进展。PI3K/Akt/mTOR 通路调节癌症中的几种细胞功能,如细胞生长、存活和增殖。此外,PI3K/Akt/mTOR 通路的高激活水平与对常规化疗和激素治疗的耐药性有关。mTOR 抑制剂依维莫司与激素治疗联合使用,在转移性乳腺癌患者中取得了无进展生存期的优异结果,这些患者对激素治疗耐药。因此,依维莫司已被纳入国家综合癌症网络(NCCN)指南 2012 年版,其与依西美坦的联合应用最近已被美国食品和药物管理局和欧洲药品管理局批准。这是首次批准用于恢复乳腺癌激素敏感性的药物。